Alkoxybenzyl cyanides, such as 4-(2-methoxyethoxy)-benzyl cyanide, are active ingredient intermediates which make a series of subsequent products, such as the corresponding phenylacetic acids, amides and amines, accessible. For 2-(4-(2-methoxyethoxy)-phenyl)-ethylamine, which is readily obtainable from 4-(2-methoxyethoxy)-benzyl cyanide, uses as a building block in the synthesis of pharmacologically effective substances are known (WO 98/37079). However, the synthesis of this amine has hitherto not been described in the literature. The 4-(2-methoxyethoxy)-benzyl cyanide according to the invention permits simple access to this synthesis building block.
It is known that 3- and 4-(2-methoxyethoxy)-benzaldehyde can be prepared by boiling at reflux 3- or 4-hydroxybenzaldehyde respectively with 2-chloroethyl methyl ether in dimethylformamide in the presence of potassium carbonate. This gives yields of 60.5 and 75.5% of theory respectively (see J. Med. Chem. 25, 440 (1982) method B). A disadvantage is firstly the at times unsatisfactory yield and, secondly, the use of a costly strong polar solvent, which requires considerable expenditure with respect to industrial hygiene and cannot be completely recycled.
In a process for the preparation of 2-methoxyethoxy-benzene (referred to there as 1-methyl-4-phenyl-ethylene glycol), phenol is reacted with 2-bromoethyl methyl ether in acetonitrile, also a costly strong polar solvent, in the presence of potassium carbonate by boiling at reflux (see Can. J. Chem. 73, 572 (1995)). In addition to the expenditure for the provision of the bromine compound and the disadvantages arising by virtue of the use of acetonitrile (which are similar to those in the case of the use of dimethylformamide), the yield achieved of only 26% is entirely unsatisfactory.
There is therefore still a need for a process for the preparation of 2-methoxyethoxybenzenes which produces the desired products in good yields in a simple and cost-effective manner.